The purpose of this competitive renewal is: 1) To move our study of neuroplasticity-based cognitive training in schizophrenia out of the laboratory and into the community setting; 2) To demonstrate its specific utility as a method for restoring cognition and enhancing functional outcome in schizophrenia patients referred to a community-based supported employment (SE) program. In our neuroscience-based cognitive training program, the user must successfully perform thousands of progressively more difficult learning trials that improve signal-to-noise processing in early sensory, attention, and working memory functions. The goal is to foster the recovery of key neurocognitive functions by harnessing mechanisms of brain plasticity under constrained and carefully controlled conditions, rather than to promote the development of compensatory cognitive or behavioral operations. Data from our current laboratory-based randomized controlled trial (RCT) indicate that, after 50 hours of training and relative to an active control, individuals with schizophrenia show significant improvements in processing speed, working memory, and verbal learning and memory (effect size of 1.0). Gains endure 6 months after training and are significantly associated with improvement in measures of social and occupational functioning and motivation. Active training subjects also show significant increases in serum BDNF levels. In order for this restorative cognitive remediation approach to have a meaningful impact on the well- being and recovery of individuals with schizophrenia, our next phase of research must answer three critical questions: Can neuroplasticity-based computerized targeted cognitive training (TCT) be implemented in real- world clinical settings? Does it enhance patients' response to psychosocial rehabilitation (in the form of SE), significantly improving functional outcome? Does it offer patients specific gains in terms of neurocognition and functioning in the context of SE? To answer these questions, we will perform an RCT of 100 hours of neuroplasticity-based TCT vs. an active control condition (100 hours of graphically interesting computer games), when combined with SE for participants with chronic schizophrenia. The study will take place in an urban community mental health center in downtown San Francisco. Both subject groups will be comparable in terms of amount of research staff contact and computer exposure, and will differ only in whether or not they receive an active neuroplasticity- based cognitive training approach. Subjects will be assessed at baseline, and at 6 and 12 months on the primary outcome measures of neurocognition. They will be assessed at 6, 12, 18 and 24 months on secondary outcomes of employment and quality of life. PUBLIC HEALTH RELEVANCE: This purpose of this study is to investigate the usefulness of neuroscience-guided cognitive training combined with community-based supported employment for people with schizophrenia. We will examine the effectiveness of moving our study of neuroplasticity-based restorative targeted cognitive training out of the laboratory and into the community setting; and we will also investigate its utility in enhancing functional outcome in chronically mentally ill adults who are participating in supported employment.